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BioMed Research International
Volume 2014, Article ID 708903, 17 pages
http://dx.doi.org/10.1155/2014/708903
Research Article

Antioxidant Defense Enzyme Genes and Asthma Susceptibility: Gender-Specific Effects and Heterogeneity in Gene-Gene Interactions between Pathogenetic Variants of the Disease

1Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, 3 Karl Marx Street, Kursk 305041, Russia
2Department of Pediatrics, Kursk State Medical University, 11a Koltsov Street, Kursk 305035, Russia
3Research Institute for Medical Genetics, Siberian Branch of Russian Academy of Medical Sciences, 10 Nabereznaya Ushaiki Tomsk 634050, Russia
4Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1, 85764 Neuherberg, Germany
5Hanover Unified Biobank, Hanover Medical School, Carl-Neuberg-Strasse 1, 30625 Hanover, Germany

Received 23 February 2014; Revised 5 April 2014; Accepted 7 April 2014; Published 5 May 2014

Academic Editor: Siyuan Zheng

Copyright © 2014 Alexey V. Polonikov et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Oxidative stress resulting from an increased amount of reactive oxygen species and an imbalance between oxidants and antioxidants plays an important role in the pathogenesis of asthma. The present study tested the hypothesis that genetic susceptibility to allergic and nonallergic variants of asthma is determined by complex interactions between genes encoding antioxidant defense enzymes (ADE). We carried out a comprehensive analysis of the associations between adult asthma and 46 single nucleotide polymorphisms of 34 ADE genes and 12 other candidate genes of asthma in Russian population using set association analysis and multifactor dimensionality reduction approaches. We found for the first time epistatic interactions between ADE genes underlying asthma susceptibility and the genetic heterogeneity between allergic and nonallergic variants of the disease. We identified GSR (glutathione reductase) and PON2 (paraoxonase 2) as novel candidate genes for asthma susceptibility. We observed gender-specific effects of ADE genes on the risk of asthma. The results of the study demonstrate complexity and diversity of interactions between genes involved in oxidative stress underlying susceptibility to allergic and nonallergic asthma.